When compared with bilateral biliary drainage, unilateral biliary drainage is associated with a lower incidence of liver abscess as well as a comparable outcome of stent patency time and complication-free survival. We therefore propose that hilar biliary obstruction can be treated first by unilateral drainage with a metallic stent and by bilateral drainage only in patients who develop cholangitis in the contralateral biliary tree.

The role of bacterial capsule in in¯ammatory responses in experimentally induced pneumonia caused by Klebsiella pneumoniae was evaluated by comparing the host immunological responses in mice infected with capsulate strain DT-S and non-capsulate mutant strain DT-X. Anaesthetised ICR mice were infected intranasally with inocula of strain DT-S or DT-X. Mice infected with strain DT-X survived signi®cantly longer than those inoculated with strain DT-S. Viable bacterial counts in lungs and blood increased rapidly in mice infected with strain DT-S, in contrast to the gradual decrease in their density in lungs and intermittent bacteraemia in mice infected with strain DT-X. The number of broncho-alveolar lavage (BAL) cells in mice infected with strain DT-X at 24 h after inoculation was signi®cantly higher than in those infected with strain DT-S. In the early stages of infection, the levels of tumour necrosis factor-á and interleukin-6 in BAL uid of mice infected with strain DT-X were signi®cantly higher than those of mice infected with strain DT-S. In contrast, in the late stage of infection, the levels of these cytokines in serum of mice infected with strain DT-S were signi®cantly higher than in mice infected with strain DT-X. These results suggest that K. pneumoniae capsule may suppress the host immunological responses, thus allowing the bacteria to grow, causing pneumonia, septicaemia and death.

ASM of the hip joint is a reliable early biomarker of radiographic OA severity, which can improve the ability to identify patients at higher risk of rapid progression and poor outcome even when KLG and clinical risk factors are taken into account.

The role of the capsule of Klebsiella pneumoniae in inducing cytokine production was investigated by comparing the responses of mice with experimentally induced pneumonia caused by capsulate (strain DT-S) or non-capsulate (mutant strain DT-X) K. pneumoniae. Anaesthetised ICR mice were inoculated intranasally. Whereas all DT-S-infected mice died within 3 days, no deaths were observed in DT-X-infected mice by 14 days after infection. During the early stage of infection, interferon-ã (IFN-ã) levels in bronchoalveolar lavage¯uid (BALF) of DT-X-infected mice were signi®cantly higher than those in DT-S-infected mice. In contrast, in the late stage of infection, serum levels of granulocyte macrophage-colony stimulating factor (GM-CSF) and IFN-ã in DT-Sinfected mice were signi®cantly higher than those in DT-X-infected mice. Levels of interleukin-10 (IL-10) in BALF and serum of DT-S-infected mice were signi®cantly and persistently higher than those of DT-X-infected mice. The IL-10=TNF-á (tumour necrosis factor-á) ratios in BALF and serum indicated that higher levels of IL-10 production were induced in mice infected with strain DT-S than in those infected with strain DT-X. The results suggest that the capsule of K. pneumoniae may induce IL-10 production at the site of infection and, thereafter, these high IL-10 levels may serve to down-regulate the expression of pro-in¯ammatory cytokines.

No abstract

The study was designed to determine the role of interferon (IFN)-ã in in¯ammatory responses against experimentally induced pneumonia caused by Klebsiella pneumoniae. The host immunological responses in IFN-ã gene knockout (IFN-ã 2=2 ) mice and immunocompetent control mice were compared. K. pneumoniae strain T-113 was inoculated intranasally into anaesthetised mice to induce pneumonia. Infected control mice survived signi®cantly longer than infected IFN-ã 2=2 mice. Viable bacterial counts in lungs and blood abruptly increased in IFN-ã 2=2 mice; in contrast, a gradual decrease in the number of bacteria was noted in control mice. During the early stages of infection, the concentrations of interleukin (IL)-1â and IL-6 in broncho-alveolar lavagē uid and IL-1â in serum of IFN-ã 2=2 mice were signi®cantly lower than in control mice. During the late stage of infection, serum IL-6 level in IFN-ã 2=2 mice was signi®cantly higher than in control mice. These results suggest that the defective immunological host response, including in¯ammatory cytokine production caused by de®ciency of IFN-ã, is one of the mechanisms that allow the progression of pulmonary infection to systemic septicaemia.

In this study, we found Cystatin SN (CST1), a type 2 cystatin subfamily member, to be highly expressed in nasal polyps from patients with intractable chronic rhinosinusitis (CRS) with nasal polyps, using a whole-transcript analysis with next-generation sequencing. Eosinophilic CRS (ECRS) involves nasal polyps that are refractory and recur immediately after endoscopic sinus surgery. We hypothesized that CST1 may contribute to the pathogenesis of ECRS. We examined the expression of CST1 in nasal polyps from patients with ECRS by assessing mRNA expression levels using real-time PCR and immunohistochemistry. CST1 showed significantly greater expression in the epithelial cells of nasal polyps from patients with ECRS than in those from patients who did not have ECRS (non-ECRS). In particular, CST1 showed very strong expression in patients with severe ECRS. The expression of CST1 may be correlated with the recurrent and refractory nature of ECRS. We examined the function of CST1 using nasal epithelial cells and nasal fibroblasts. Stimulation by a combination of IL-4 plus double-stranded RNA plus CST1 significantly elevated mRNA expression levels and protein levels of TSLP in nasal epithelial cells. Stimulation by TSLP or IL-33 significantly elevated mRNA expression levels of CST1 in nasal epithelial cells. Stimulation of CST1 significantly elevated mRNA expression levels of CCL11 and POSTN in nasal fibroblasts. CST1 could amplify eosinophilic infiltration and T-helper cell type 2 inflammation by interacting with epithelial-derived cytokines and fibroblasts on nasal polyps. CST1 may be involved in the pathogenesis of ECRS, and may contribute to the severity and recurrence of CRS with nasal polyps after endoscopic sinus surgery.

Recently, the MICA rs2596542 and DEPDC5 rs1012068 variants in Japanese individuals as well as the HCP5 rs2244546 and PNPLA3 rs738409 variants in European individuals have been found associated with hepatocellular carcinoma (HCC). The present study determined which single nucleotide polymorphism (SNP) is the most predictive for developing hepatitis C virus (HCV)-related HCC in a Japanese cohort. Of the 4 SNPs analysed, only the MICA genotypes were significantly associated with development of HCC (p = 0.0185). The major (MA), hetero (HE), and minor (MI) genotypes occurred in 40%, 41%, and 19% of HCC patients and in 43%, 47%, and 10% of non-HCC patients, respectively. Interestingly, the MICA genotype was significantly correlated with MICA mRNA and soluble protein levels. In patients older than 70 years, the MI genotype was significantly associated with HCC development. In addition, the MI genotype was related to HCC development when the platelet count range was 10–15 × 104/μL, corresponding with the fibrosis stage; but not when the range was less than 10, indicating advanced fibrosis; or greater than 15 × 104/μL, as mild fibrosis. Thus, polymorphisms in MICA, but not in DEPDC5, HCP5 or PNPLA3, are associated with HCC development in Japanese patients with chronic HCV infection.